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== '''Overall project''' == | == '''Overall project''' == | ||
| - | + | While pharmaceutical companies rely on many model systems for the development and testing of candidates, these systems often are not predictive of actual efficacy and toxicity in patients. An ideal system for drug development would recapitulate in vivo responses in a scalable fashion. | |
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| + | One promising approach is the creation of engineered tissues via genetic reprogramming. A cell programmed with a synthetic gene network could multiply and give rise to synthetic tissues comprised of multiple cell types. While there has been some success in engineering genetic circuits within mammalian cells, most of these circuits function in single cells independent of the global population. The formation of predictable complex structures and engineered multicellular tissues requires coordinated behavior among populations of cells. | ||
== Project Details== | == Project Details== | ||
| + | This year, the MIT iGEM team is working to develop circuits that implement multiplexed cell-cell communication mediated by exosomes in mammalian cells. Our approach is to incorporate two parallel signaling strategies using exosomes: small miRNA and a Cas9 complex. | ||
| + | === miRNA Signaling === | ||
| + | In the first strategy, we utilize miRNA that are selectively targeted into exosomes. Sender cells produce exosomes with our miRNA signals. These exosomes carry signals to engineered receiver cells that use these miRNA inputs to modulate gene expression. | ||
| + | ==== The Experiments ==== | ||
| - | === | + | === Protein Signaling=== |
| + | The second signaling strategy employs proteins contained within exosomes. We fuse targeting motifs to a CAS9-VP16 protein resulting in selective exosomal partitioning of this species in sender cells. In receiver cells, this signal modulates gene expression through the Cas9-CRISPR mechanism with a variable guide RNA. | ||
| + | ==== The Experiments ==== | ||
| + | == Results == | ||
| + | == Applications == | ||
| - | + | Successful completion of our project would enable a localized, controllable system to induce changes in cellular surroundings for use in pharmaceutical research. Our populations would function as engineered tissues or ‘organoids’ for rapid screening and development of drugs. | |
| - | + | Additionally, because the Cas9-CRISPR mechanism does not require engineered receiver cells, this may enable a new strategy for gene therapy and cell re-programming. | |
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Revision as of 04:06, 5 July 2013
| Home | Team | Official Team Profile | Project | Parts Submitted to the Registry | Modeling | Notebook | Safety | Attributions |
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Contents |
Overall project
While pharmaceutical companies rely on many model systems for the development and testing of candidates, these systems often are not predictive of actual efficacy and toxicity in patients. An ideal system for drug development would recapitulate in vivo responses in a scalable fashion.
One promising approach is the creation of engineered tissues via genetic reprogramming. A cell programmed with a synthetic gene network could multiply and give rise to synthetic tissues comprised of multiple cell types. While there has been some success in engineering genetic circuits within mammalian cells, most of these circuits function in single cells independent of the global population. The formation of predictable complex structures and engineered multicellular tissues requires coordinated behavior among populations of cells.
Project Details
This year, the MIT iGEM team is working to develop circuits that implement multiplexed cell-cell communication mediated by exosomes in mammalian cells. Our approach is to incorporate two parallel signaling strategies using exosomes: small miRNA and a Cas9 complex.
miRNA Signaling
In the first strategy, we utilize miRNA that are selectively targeted into exosomes. Sender cells produce exosomes with our miRNA signals. These exosomes carry signals to engineered receiver cells that use these miRNA inputs to modulate gene expression.
The Experiments
Protein Signaling
The second signaling strategy employs proteins contained within exosomes. We fuse targeting motifs to a CAS9-VP16 protein resulting in selective exosomal partitioning of this species in sender cells. In receiver cells, this signal modulates gene expression through the Cas9-CRISPR mechanism with a variable guide RNA.
The Experiments
Results
Applications
Successful completion of our project would enable a localized, controllable system to induce changes in cellular surroundings for use in pharmaceutical research. Our populations would function as engineered tissues or ‘organoids’ for rapid screening and development of drugs.
Additionally, because the Cas9-CRISPR mechanism does not require engineered receiver cells, this may enable a new strategy for gene therapy and cell re-programming.
